The next phase of this ongoing research will address the mechanisms which affect heterogeneity in the lungs. Building on previous work in this program, the focus of the proposed program is on the mechanisms of heterogeneity of ventilation and perfusion in the lungs. The projects deal either with ventilation or perfusion separately, the matching of the two as it affects gas exchange and influences on edema formation. The approach is multidisciplinary, with investigators trained in medicine, physiology, anesthesiology, morphology, engineering and radiology. It is a result of two decades of interest in pulmonary physiology and medicine and collaboration between the investigators. The program is designed to support other research, particularly in ARDS and pulmonary vascular disease, which is proceeding at this institution. The strengths of the proposal include the integration of many disciplines, the productivity of this group of investigators and the expansion of experimental approaches using imaging, fluorescent microspheres, tissue diffusion cells, and aerosol assessment of ventilation heterogeneity. The outcome should be a more complete understanding of the mechanisms by which the lungs respond to perturbations in ventilation and perfusion distribution both in health and disease.